FDA Review of Drugs and Medical Devices: What You Need To Know

Prescription drugs and most medical devices are reviewed by the Food and Drug Administration (FDA) before they can be marketed in the United States.[1],[2] The FDA provides several approval pathways for manufacturers that differ not only between drugs and medical devices, but also within each of these categories.

The various requirements can be confusing, and according to a recent survey, even many physicians feel they don’t know enough about the different FDA approval pathways.[3] This article discusses the main points you need to know about how the FDA reviews drugs and medical devices.

The drug approval process

The FDA does not conduct its own clinical trials to approve prescription drugs. Instead, the agency reviews data that sponsors, usually pharmaceutical companies, submit to the agency in support of their drug approval applications.[4] Often, pharmaceutical companies conduct these trials in collaboration with academic clinical investigators who have access to potential research subjects through the hospitals or outpatient clinics where they work.

As a first step in gathering the necessary data, manufacturers test a potential new drug in a preclinical laboratory setting and sometimes in animal studies as well.[5],[6] If these preliminary tests show that the drug appears to be safe, it can then be tested in humans.

Trial design can vary considerably between drugs and diseases. Typically, manufacturers first conduct Phase 1 studies in a small number of healthy volunteers to assess the drug’s effects on the human body and whether, on initial testing, the potential adverse effects are acceptable. Next, Phase 2 studies are conducted to test the drug’s effectiveness in a few hundred subjects who have the disease the medication is meant to treat. Finally, the safety and effectiveness of the new drug is tested in one or more large-scale Phase 3 studies, which can include several hundred to several thousand subjects with the disease.

The FDA generally requires the results of two adequate and well-controlled clinical trials for a traditional drug approval, with clinical endpoints such as whether patients who receive the drug live longer or are less likely to be hospitalized than those who receive another drug or a placebo. In some cases, however, the agency can grant approval based on less robust outcome data through different pathways.[7] For example, if a newly developed drug treats a rare disease or would fill an unmet medical need in the treatment of a life-threatening condition, approvals can be expedited (for instance, through “accelerated approval”).

A faster approval can be granted based on the results of one clinical trial and confirmatory evidence or trials that use “surrogate endpoints.” Such surrogate endpoints may include physical signs or laboratory findings that are considered “reasonably likely to predict clinical benefit” but do not directly measure the clinical benefit of a drug.

If the FDA concludes that the data provided by the manufacturer has demonstrated that the drug is safe and effective — that is, that its benefits outweigh the known harms — and there are no other issues, the drug is generally approved.[8] In some situations, when a drug is the first of its kind or the data are inconclusive or raise safety concerns that require careful consideration, the FDA may convene an advisory committee meeting and seek the advice of independent experts before reaching a decision.

Once a drug is approved, the FDA continues to monitor the safety and effectiveness of the drug, for example through the FDA’s Adverse Event Reporting System, and can require updates in the prescribing information of the drug.[9] In some instances, the FDA requires the manufacturer to conduct post-approval studies to provide more information about a drug’s safety and effectiveness.

The approval process for generic and over-the-counter medications is generally less complex. Manufacturers usually are not required to conduct clinical trials to test the safety and effectiveness of these kinds of drugs.[10] Because generic drugs are copies of already approved drugs, a manufacturer mainly needs to demonstrate that a new generic is “bioequivalent” to an already approved drug (meaning that it has the same amount of the active ingredient and has the same effects as the brand-name drug). The FDA establishes that manufacturers of over-the-counter drugs have followed the FDA’s “recipe book,” which includes a list of acceptable ingredients, formulations, doses and labeling permitted for over-the-counter drugs.[11]

The medical device approval and clearance process

For medical devices, the FDA bases its level of regulatory control on the risk associated with the device.[12] Medical devices that “support or sustain life, are implanted in the body, or have the potential for unreasonable risk of illness or injury,” such as mechanical heart valves, implantable infusion pumps, or pacemakers, are considered high-risk, or Class III, devices. Devices in this category can only be sold if they pass the FDA’s “premarket approval” pathway,[13] for which manufacturers need to demonstrate the safety and effectiveness of the device in clinical trials.

For medical devices that are not considered to be high risk, manufacturers usually do not need to provide clinical data on the safety and effectiveness of the device.[14] For instance, moderate-risk (Class II) devices, a class that includes powered wheelchairs, certain pregnancy kits or dialysis equipment, can be cleared for marketing through two pathways. If manufacturers can demonstrate that their new device is “substantially equivalent” to another device that is already on the market (called a predicate), the new device can be cleared for marketing through a “premarket notification” or 510(k) pathway.[15] Many more devices are cleared through the 510(k) pathway than through premarket approval, and only about 8% of applications for Class II devices include any clinical data.[16] If there are no predicate devices that can be used for clearance, manufacturers need to demonstrate the devices’ safety and effectiveness through a less common pathway called “De Novo classification request.”

Medical devices that are considered low risk are referred to as Class I devices; FDA oversight of such devices is limited. Class I devices are usually exempt from regulatory review. Examples of Class I devices include elastic bandages, oxygen masks or exam gloves.

Concerns about drug and device approvals

The FDA approved or cleared on average about 46 novel drugs each year from 2014 to 2023 and 73 medical devices each year from 2009 to 2020, although in recent years the number of annual approvals has steadily increased.[17],[18] However, many of these approvals are based on low-quality evidence.[19] At present, almost half of prescription drugs are approved based on data from one trial instead of the gold standard of two adequate and well-controlled clinical trials. Drug approvals are increasingly based on surrogate endpoints instead of trials demonstrating measurable clinical benefit. For devices, although the FDA states that the 510(k) clearance pathway has few risks,[20] between 2008 and 2017 the agency recalled about 11% of such devices, including several that were subject to a Class I recall, the FDA’s most serious recall designation for serious harm or death.[21]

A 2011 report by the National Academy of Medicine (then called the Institute of Medicine) concluded that the 510(k) process is “not a determination that the cleared device was safe or effective.”[22] Of particular concern is that manufacturers can base their application on predicate devices that have established safety issues. For instance, almost half of the cleared devices that were subject to a Class I recall between 2017 and 2021 were based on predicate devices that had themselves been previously subject to such a recall.[23] Although the 510(k) pathway is currently under review, as of November 2024 the FDA was still considering whether to make any changes.[24]

What You Can Do

All prescription drugs and some medical devices that are marketed in the United States have been reviewed by the FDA to ensure that they are effective and that their benefits outweigh potential harms. The prescribing information for a particular product will state whether it has been approved or cleared by the FDA.[25] Certain products, such as compounded drugs and herbal or dietary supplements, are not approved or reviewed by the FDA.[26]

Moreover, just because a product is approved or cleared by the FDA does not mean that it is right for you or safe for you to use. Always consult your clinician about whether a prescription drug or medical device is the right choice for you.
 

References

[1] National Institutes of Health. How are drugs approved for use in the United States? December 20, 2021. https://www.nichd.nih.gov/health/topics/pharma/conditioninfo/approval. Accessed November 4, 2024.

[2] Food and Drug Administration. Learn if a medical device has been cleared by FDA for marketing. December 29, 2017. https://www.fda.gov/medical-devices/consumers-medical-devices/learn-if-medical-device-has-been-cleared-fda-marketing. Accessed November 4, 2024.

[3] Dhruva SS, Kesselheim AS, Woloshin S, et al. Physicians' perspectives on FDA regulation of drugs and medical devices: a national survey. Health Aff. 2024;43(1):27-35.

[4] Food and Drug Administration. Development and approval process: drugs. August 8, 2022. https://www.fda.gov/drugs/development-approval-process-drugs. Accessed November 4, 2024.

[5] Food and Drug Administration. The FDA's drug review process: Ensuring drugs are safe and effective. November 24, 2017. https://www.fda.gov/drugs/information-consumers-and-patients-drugs/fdas-drug-review-process-ensuring-drugs-are-safe-and-effective. Accessed November 4, 2024.

[6] Science. FDA no longer needs to require animal tests before human drug trials. January 10, 2023. https://www.science.org/content/article/fda-no-longer-needs-require-animal-tests-human-drug-trials. Accessed November 5, 2024.

[7] Food and Drug Administration. Development and approval process: drugs. August 8, 2022. https://www.fda.gov/drugs/development-approval-process-drugs. Accessed November 4, 2024.

[8] Food and Drug Administration. FDA's drug review process: continued. August 24, 2015. https://www.fda.gov/drugs/information-consumers-and-patients-drugs/fdas-drug-review-process-continued. Accessed November 4, 2024.

[9] Food and Drug Administration. Sociodemographic characteristics of adverse event reporting. March 1, 2024. https://www.fda.gov/drugs/spotlight-cder-science/sociodemographic-characteristics-adverse-event-reporting?utm_medium=email&utm_source=govdelivery. Accessed November 4, 2024.

[10] Food and Drug Administration. Generic drugs: Questions & answers. March 16, 2021. https://www.fda.gov/drugs/frequently-asked-questions-popular-topics/generic-drugs-questions-answers. Accessed November 4, 2024.

[11] Food and Drug Administration. How drugs are developed and approved. October 24, 2022. https://www.fda.gov/drugs/development-approval-process-drugs/how-drugs-are-developed-and-approved. Accessed November 4, 2024.

[12] Food and Drug Administration. Step 1: Device discovery and concept. January 4, 2018. https://www.fda.gov/patients/device-development-process/step-1-device-discovery-and-concept. Accessed November 4, 2024.

[13] Food and Drug Administration. Is it really 'FDA approved'? May 10, 2022. https://www.fda.gov/consumers/consumer-updates/it-really-fda-approved. Accessed November 4, 2024.

[14] Ibid.

[15] Kadakia KT, Rathi VK, Dhruva SS, et al. Modernizing medical device regulation: challenges and opportunities for the 510(k) clearance process. Ann Intern Med. doi: 10.7326/ANNALS-24-00728. Published online ahead of print October 8, 2024.

[16] Institute of Medicine. Medical devices and the public’s health: the FDA 510(k) clearance process at 35 years. July 29, 2011. https://nap.nationalacademies.org/catalog/13150/medical-devices-and-the-publics-health-the-fda-510k-clearance. Accessed November 4, 2024.

[17] Food and Drug administration. New drug therapy approvals 2023. January 2024. https://www.fda.gov/media/175253/download?attachment. Accessed November 4, 2024.

[18] Food and Drug Administration. Reflections on a record year for novel device innovation despite COVID-19 challenges. February 16, 2021. https://www.fda.gov/news-events/fda-voices/reflections-record-year-novel-device-innovation-despite-covid-19-challenges. Accessed November 4, 2024.

[19] Darrow JJ, Avorn J, Kesselheim AS. FDA approval and regulation of pharmaceuticals, 1983-2018. JAMA. 2020;323(2):164-176.

[20] Food and Drug Administration. Medical device safety and the 510(k) clearance process. September 6, 2023. https://www.fda.gov/medical-devices/510k-clearances/medical-device-safety-and-510k-clearance-process. Accessed November 4, 2024.

[21] Dubin JR, Simon SD, Norrell K, et al. Risk of recall among medical devices undergoing US Food and Drug Administration 510(k) clearance and premarket approval, 2008-2017. JAMA Netw Open. 2021;4(5):e217274.

[22] Institute of Medicine. Medical devices and the public’s health: The FDA 510(k) clearance process at 35 years. July 29, 2011. https://nap.nationalacademies.org/catalog/13150/medical-devices-and-the-publics-health-the-fda-510k-clearance. Accessed November 4, 2024.

[23] Kadakia KT, Dhruva SS, Caraballo C, et al. Use of recalled devices in new device authorizations under the US Food and Drug Administration's 510(k) pathway and risk of subsequent recalls. JAMA. 2023;329(2):136-143.

[24] Kadakia KT, Rathi VK, Dhruva SS, et al. Modernizing medical device regulation: Challenges and opportunities for the 510(k) clearance process. Ann Intern Med. doi: 10.7326/ANNALS-24-00728. Published online ahead of print October 8, 2024. See the following link for the still open/ non finalized guidance: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommendations-use-clinical-data-premarket-notification-510k-submissions

[25] National Institutes of Health. How are drugs approved for use in the United States? December 20, 2021. https://www.nichd.nih.gov/health/topics/pharma/conditioninfo/approval. Accessed November 4, 2024.

[26] Food and Drug Administration. Is it really 'FDA approved'? May 10, 2022. https://www.fda.gov/consumers/consumer-updates/it-really-fda-approved. Accessed November 4, 2024.